Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain
2020 | journal article; research paper
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Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain
Mukherjee, C.; Kling, T.; Russo, B.; Miebach, K.; Kess, E.; Schifferer, M. & Pedro, L. D. et al. (2020)
Cell Metabolism, 32(2) pp. 259.e10-272.e10. DOI: https://doi.org/10.1016/j.cmet.2020.05.019
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Details
- Authors
- Mukherjee, Chaitali; Kling, Tina; Russo, Belisa; Miebach, Kerstin; Kess, Eva; Schifferer, Martina ; Pedro, Liliana D.; Weikert, Ulrich; Fard, Maryam K.; Kannaiyan, Nirmal; Rossner, Moritz; Aicher, Marie-Louise; Goebbels, Sandra; Nave, Klaus-Armin ; Krämer-Albers, Eva-Maria; Schneider, Anja; Simons, Mikael
- Abstract
- An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secretion pathway involving extracellular vesicles. Disrupting the release of extracellular vesicles or the expression of ferritin heavy chain in oligodendrocytes causes neuronal loss and oxidative damage in mice. Our data point to a role of oligodendrocytes in providing an antioxidant defense system to support neurons against iron-mediated cytotoxicity.
- Issue Date
- 2020
- Journal
- Cell Metabolism
- Project
- TRR 274: Checkpoints of Central Nervous System Recovery
TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis - Working Group
- RG Nave (Neurogenetics)
RG Schifferer
RG Simons (The Biology of Glia in Development and Disease) - ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English